Microfluidic device and manufacture thereof

ABSTRACT

The present invention relates to microfluidic devices and to their method of manufacture. The microfluidic devices are original by their specific structure (of sandwich type) and by the materials from which they are made (mainly glasses, glass ceramics, ceramics), and also by their specific method of manufacture, which is based on a vacuum-forming operation. The microfluidic device includes a first assembly including a microstructure and a first substrate, wherein the microstructure is constructed and arranged on the substrate under vacuum. A second assembly includes a second substrate positioned on the microstructure after the first assembly is presintered and adhered thereto by heat treatment to form a one-piece microstructure defining at least one recess between the first and second substrates.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of co-pending U.S. patent applicationSer. No. 10/163,215 filed on Jun. 4, 2002, now U.S. Pat. No. 6,595,232the content of which is relied upon and incorporated herein by referencein its entirety, which claims the benefit of French Patent ApplicationNo. 01 12500, filed on Sep. 28, 2001, in the names of Guillermo Guzmanand Jean-Pierre Themont, the entire content of which is incorporatedherein by reference, and the benefits of priority under 35 U.S.C. § 119and § 120 are hereby claimed.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates generally to: the field of microreactorsand more particularly to a microfluidic device and a method ofmanufacturing such microfluidic devices.

2. Technical Background

Microfluidic devices are structures familiar to those skilled in theart, structures for which numerous applications have already beendescribed, in particular in references such as: MicroreactionTechnology, 3^(rd) International Conference on Microreaction Technology;edited by W. Ehrfeld, published by Springer-Verlag, Berlin (2000); andMicro-total Analysis Systems 2000, edited by A. Van Den Berg, W.Olthius, and P. Bergveld, published by Kluwer Ac Publishers (2000).Within such structures, in volumes that are small (having acharacteristic dimension that generally lies in the range of 10micrometers (μm) to 1000 μm), fluids are directed and/or mixed togetherand/or caused to react.

Such devices known in the art include, microfluidic devices made ofvarious types of material, and in particular of polymers, of silicon, orof metals. The shortcomings encountered with those materials arenumerous. For example, devices made of polymers cannot withstandtemperatures of more than 200° C. to 300° C. over a prolonged period.Moreover, it is often difficult to control surface states effectivelywithin such structures.

Silicon devices are expensive, incompatible with certain biologicalfluids, and the semiconductive nature of silicon gives rise to problemswith implementing certain pumping techniques, such aselectro-hydrodynamic pumping and electro-osmotic pumping.

Devices made of metal are liable to corrode, and in like manner they aretypically not compatible with certain biological fluids.

It has therefore been found desirable, in numerous contexts, to havefluidic microstructures made of glass, glass ceramic, or ceramic. Thosematerials are particularly appreciated for their insulating nature(thus, U.S. Pat. No. 6,210,986 describes the benefit of havinginsulating structures available when the fluid is moved byelectro-osmosis or by electrokinetics), for their resistance or eveninertness in the face of chemical attack, for their transparency, fortheir surface homogeneity, and for the ease with which their surfacescan be modified chemically. Microfluidic devices made of glass have beenobtained by chemical or physical etching. Those etching technologiesgive rise to hollows in a glass substrate and they are not entirelysatisfactory to implement. Isotropic chemical etching does not enablesignificant aspect ratios to be obtained, while physical etching isdifficult to implement, in particular because of its high cost andlimited production capacity. To close such open structures, thetechnique most often employed is ionic attachment. That technique isexpensive, and difficult to implement insofar as it is highly sensitiveto dust and insofar as the surface of each layer that is to come intocontact must be as flat as possible in order to provide high qualitysealing.

Microfluidic devices made of ceramic, as described in European patentapplication No. EP-A-0 870 541, generally are obtained by ceramizing astack of ceramizable layers (green mixture of ceramic powders and anorganic binder). In the stack, there is no support layer, and withineach ceramizable layer the empty volume remains limited.

In another context, that of screens and digital displays, the followingtechniques have been described. Generally speaking, glass formingoperations to generate rectilinear parallel ribs on a flat support areknown in the art. Unlike the method of the present invention, suchforming steps are not performed in a vacuum. Known techniques are wellrepresented in U.S. Pat. No. 5,853,446.

Operations for closing open plane structures having rectilinear parallelribs, such as those obtained by the above-mentioned forming operationsare also known. In accordance with such forming operations, a fine layerof glass paste is placed on these ribs, which are not too far apart.This is described in Japanese application No. JP-A-12 187 028. Thetechnique incorporating the fine layer of glass cannot in any way beconsidered to be equivalent to the support substrate of devices made inaccordance with the present invention.

What is needed therefore, but presently unavailable in the art, is amicrofluidic device and method of manufacturing such a microfluidicdevice that overcomes these and other shortcomings associated with theuse and manufacture of microfluidic devices known in the art. Suchmicrofluidic devices should be capable of obtaining high aspect ratios,and should be well suited for use as microreactors for the chemical,pharmaceutical, and biotechnology industries. The method ofmanufacturing such microfluidic devices should be compatible with lowcost production while at the same time provide advantageous yields. Itis to the provision of such a microfluidic device and method ofmanufacturing such microfluidic devices that the present invention isprimarily directed.

SUMMARY OF THE INVENTION

One aspect of the present invention relates to a microfluidic device.The microfluidic device includes a first assembly including amicrostructure and a first substrate, wherein the microstructure isconstructed and arranged on the substrate under vacuum. A secondassembly including a second substrate is positioned on themicrostructure after the first assembly is presintered and adheredthereto by heat treatment to form a one-piece microstructure defining atleast one recess between the first and second substrates.

In another aspect the present invention is directed to a method ofmanufacturing a microfluidic device. The method includes the steps ofdisposing a mixture including an organic binder and a precursor materialbetween a mold and a first substrate, heating the mixture under vacuumat a temperature sufficient to thermoform the mixture onto the firstsubstrate and in the shape of the mold, and presintering thethermoformed mixture in the substrate to form a consolidated firstassembly. The first assembly is assembled with a second assemblyincluding a second substrate such that the presintered thermoformedmixture is positioned between the first presintered substrate and thesecond assembly. The assembled first assembly and second assembly isheated to a temperature sufficient to form a one-piece microstructuredefining at least one recess between the first and second substrates.

The microfluidic device and method of manufacturing such microfluidicdevices results in a number of advantages over other microfluidicdevices and manufacturing techniques known in the art. For example, thevacuum-forming aspect of the present invention is a technique that iscompatible with low-cost production and significant yield. In addition,vacuum-forming enables high aspect ratios without the use of expensivetechniques such as physical etching.

Additional features and advantages of the invention will be set forth inthe detailed description which follows and in part will be readilyapparent to those skilled in the art from that description or recognizedby practicing the invention as described herein.

It is to be understood that both the foregoing general description andthe following detailed description are merely exemplary of theinvention, and are intended to provide an overview or framework forunderstanding the nature and character of the invention as it isclaimed. The accompanying drawings are included to provide furtherunderstanding of the invention, illustrate various embodiments of theinvention, and together with the description serve to explain theprinciples and operation of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will now be described in a non-limiting manner in its twoaspects of a method and a device, with reference to the accompanyingfigures.

FIG. 1 schematically illustrates the various steps of a preferred methodof the present invention and depicts, likewise diagrammatically, thevarious intermediate products that are precursors for devices of thepresent invention, and also the end products, namely devices of thepresent invention. Three exemplary embodiments of the method, enablingthree different exemplary embodiments of single-element devices made bythe method are also shown.

FIGS. 2A and 2B depict exemplary devices of the invention built up froma plurality of elements.

FIGS. 3, 4, and 5 schematically depict various exemplary devices of theinvention each including a single element.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

As will be described in greater detail below, microfluidic devices ofthe present invention are original by their particular structure (of thesandwich type) by the materials constituting them, and by the particularmethod used to manufacture them, which is preferably based on avacuum-forming technique. The method of the present invention, moreover,is original and particularly advantageous in that it implements first,vacuum-forming (e.g. micromolding in a vacuum), and second,presintering. Unlike other methods, it also makes use of substrates orsupports.

Referring now to the first aspect of the present invention, i.e.original microfluidic devices, such microfluidic devices are preferablyclosed (with a “cover plate”), and depending on the embodiment concernedmay exist singly (n=1) or in combinations of a plurality of devices(n>1).

A microfluidic device of the invention includes at least one element(n≧1) (in particular it can consist of a single element or of a set ofsuch elements assembled together (where each element of the assembly canbe referred to as a module or a stage), or indeed a composite assemblycomprising at least one such element and at least one element of anothertype) which includes those, heat-sealed between two substrates, aone-piece microstructure (hence a “sandwich” type structure) in which atleast one recess is formed (of the channel, distribution chamber, or(chemical, biological, electrochemical) reaction chamber type); eachrecess of a microstructure of an element communicating with at least oneother recess of the microstructure of the element or of anothermicrostructure of another element of the device (which then includes n>1elements), and/or with the outside of the device so that within thedevice of the invention there is to be found at least one (liquid orgaseous) fluid circulation circuit communicating with the outside via atleast one inlet and one outlet.

The substrates of the component element(s) of the device of theinvention are may be manufactured from materials selected from glasses,glass ceramics, ceramics, metals, semiconductors such as silicon, and/orcombinations thereof.

The one-piece microstructure(s) preferably sandwiched between suchsubstrates is/are made of at least one material selected from glasses,glass ceramics, ceramics and combinations thereof.

The materials involved with contact between the above-listed materialsor precursors for the materials (in particular glass frit) arecompatible in terms of thermal expansion coefficients. As will bedescribed in greater detail below, this, among other things, may be doneto avoid any cracking, firstly during cooling after hot-forming andfiring of the final assembly and secondly while the device is in use.

A person skilled in the art will readily understand much of the benefitof devices of the invention. Within such devices, the fluids involvedmay come into contact only with surfaces that are under completecontrol. These may include surfaces of the material from which theone-piece microstructure is made (glass(es), glass ceramic(s),ceramic(s)), or surfaces of the material after modification. It istypically easy to modify such surfaces as they may be made active incertain contexts, for example by depositing a catalyst, and in othercontexts they may be made completely neutral, for example by coveringthem in particular in a film of polysiloxane. From this point of view,devices of the invention provide much better performance than knowndevices made of polymer or of metal. Furthermore, the structure ofdevices of the present invention is reinforced by the presence of thesubstrates.

It is explained below that these characteristics concerning thestructure and the nature of the component materials are alsoadvantageous in terms of the method of manufacturing such devices.

Devices of the invention may exist in numerous variants, implementedhomogeneously or otherwise when a plurality of elements are involved intheir structure. The one-piece microstructure between the two substrates(which can be identical or different in nature) of each element maythemselves be implemented in a plurality of variants. For example, thedevice of the invention can consist in a single element (n=1) of thekind characterized above. The device of the invention may consist in aplurality of elements (n>1) as characterized above, which elements mayoptionally be identical, and are preferably secured to one another. Inparticular, two elements may be secured to each other by using a commonsubstrate, as when they are prepared conjointly or by using a joiningmaterial (e.g. an adhesive) that withstands the temperatures at whichthe device is used. They may then be prepared in advance independentlyof each other.

When a device of the invention includes more than two elements (n>2),the elements may be all secured to one another using the firstabove-described technique, all secured to one another using the secondabove-described technique, or at least two of them may be secured toeach other using the first technique and at least two of them my besecured to each other using the second technique. Thus, the microfluidicdevice of the invention may include, a single element, a plurality ofelements, with at least two of the elements being secured to each othervia a common substrate and/or with at least two of the elements beingsecured to each other via their respective substrates (using a joiningmaterial between the substrates).

The device of the invention, whether it has one or more elements,generally presents at least one element within which both substrates aredisposed in a substantially parallel manner. Advantageously, all of thesubstrates of the assembly, having one or more elements, are disposed soas to be substantially parallel. Nevertheless, it is not in any wayimpossible for the structure of devices of the invention to includefacing element substrates that are not substantially parallel.

The device of the invention may also include at least one element havingat least one porous substrate and/or a one-piece microstructure that isporous. It can be desirable for the material constituting thesubstrate(s) to be porous in order to perform separation within thedevice, or it can be desirable for the material constituting theone-piece microstructure to be porous in order to fix a catalyst, inorder to perform a chemical reaction, in order to separate fluids, or inorder to perform filtering.

In general, devices of the invention include appropriate passages forinlet and outlet of the fluid(s) that is/are to flow within them, whichpassages are formed through their end substrates and/or through the endone-piece microstructures. Nevertheless, it is not impossible for thefluid inlet and/or outlet to be provided directly via one of therecesses in the one-piece structure opening out directly to the outside.

Assuming that the device of the invention includes a plurality ofelements, at least one passage can be provided through at least onesubstrate to provide communication between microstructure recessessituated on opposite sides of said substrate. The recesses performedwithin the one-piece microstructure of each element can be of arbitrarysection. Accordingly, they may have sections with numerous angles, thusbeing substantially square, rectangular, hexagonal or otherwiseincluding planar surfaces, they may have sections with few angles, thusbeing substantially semicircular or otherwise including only curvedsurfaces and planar surfaces, or they can have sections without angles,being substantially circular or otherwise including only curvedsurfaces. Advantageously they present sections without angles, so thatthe circulation of fluids (particularly liquids) within them may beoptimized. Most advantageously, all of them present such sectionswithout angles. In any event, said recesses are advantageously ofcontrolled shape. This provides definite advantages in terms ofpredicting the behavior and/or the reactions of fluids within the deviceby methods based on modeling the flow of the fluids.

The recesses in question may be defined by blocks of the material(s)constituting the microstructure that are entirely suitable for treatingas though they are walls. Such walls can be of constant thickness orotherwise, and in particular their thickness can be constant, tapering,or flaring (going away from one of the substrates between which themicrostructure is located).

In the context of advantageous exemplary embodiments of devices of theinvention, the microstructure(s) between the substrates is/arepreferably highly perforated, the total volume of the recesses (i.e. theempty percentage of the microstructure(s)) then being large. The emptypercentage is advantageously typically greater than 50% (said percentagenaturally being a volume percentage). Moreover, the microstructure(s)between the substrates present(s) walls between the recesses havingheight/thickness ratios (aspect ratios) preferably greater than 1, andadvantageously on the order of about 3 to 4, and most advantageouslygreater than about 6. It has been possible to obtain aspect ratiosgreater than or equal to approximately 10. Such aspect ratios generallycannot be obtained by isotropic chemical etching. Naturally, deviceshaving the above-specified characteristics form an integral part of theinvention even if they have a smaller percentage of empty volume thanspecified and/or even if the microstructure(s) present(s) aspect ratiosof less than 1.

The basic module or element of a microfluidic device of the invention(single element, elements repeated n times, identically, or withvariants) is thus characteristically a ternary structure including ahollowed-out one-piece microstructure between two substrates. Asmentioned above, the ternary structure, substrate plus one-piecemicrostructure plus substrate, may be functionalized by suitably porousmaterials, by surface treatment, or otherwise as is known in the art.For this purpose it can also include functionalization by the use ofadditional parts such as electrical conductors, electrodes, lightconductors, and the like. Such parts can be used as heater mechanisms,sensors, and the like.

Two additional parts may be incorporated in the ternary structure whileit is being made, and are generally incorporated in the one-piecemicrostructure, optionally in contact with one of the substrates, andoptionally opening out into a recess. They may also be arranged inintermediate layers provided between a substrate and a one-piecemicrostructure. One or more such intermediate layers may preferably beincluded

Devices of the invention may thus include at least one elementcontaining at least one additional part, for example a light conductor,an electrical conductor, an electrode, and/or it can have at least onerecess in the one-piece microstructure whose surface has been modified.

A second aspect of the present invention is described, in general,below. More specifically, a method of manufacturing microfluidicdevices, such as those described above, and having at least one elementpreferably includes the steps of, forming, under a vacuum (to avoidtrapping any bubbles of gas), a first mixture of an organic medium and amaterial that is a precursor for glass, glass ceramic, ceramic, or acombination thereof, on a first substrate made of a material selectedfrom glasses, glass ceramics, ceramics, metals, semiconductors such assilicon or combinations thereof. The precursor material concerned ispreferably compatible in terms of thermal expansion coefficient with thematerial constituting the first substrate. The vacuum-forming ispreferably implemented under conditions which confer at least a minimumamount of mechanical strength to the shapes generated.

The formed mixture is then preferably presintered by applyingappropriate heat treatment to the assembly including the first substrateand the formed mixture (the presintering serves to eliminate the organicmedium and to consolidate the structure). A second substrate made of amaterial selected from glasses, glass ceramics, ceramics, metals,semiconductors such as silicon or combinations thereof is thenpreferably applied, which material may be identical or different fromthat of the first substrate, the material being compatible in terms ofthermal expansion coefficient with substantially all of the precursormaterials with which it may come into contact. The second substratebeing involved may be either untreated, coated on one of its faces witha second mixture of a thermoplastic medium and a material that is aprecursor for glass, glass ceramic, ceramic, or a combination thereof,which mixture is optionally identical to that used on the firstsubstrate, is not vacuum-formed, is optionally presintered, and in anyevent is compatible with the second substrate and with the firstmixture, or indeed coated on one its faces with such a second mixturewhich has previously been vacuum-formed and presintered in succession.The two substrates may then be assembled together such that the mixturesoptionally present on each of the substrates face each other. Althoughnot required, the above operations may optionally be repeated at leastonce either identically or with variations concerning the nature of thesecond substrate, using the assembly that has already been obtained asthe bottom or top portion of a structure that includes, in succession,two, three, and/or more stages. The resulting assembly, having one ormore stages, may then be heat treated (fired) so as to bond together theprecursor material(s) and the substrates, or so as to bond the differentprecursor materials together and to each of the substrates on which theyhave been deposited.

The vacuum-forming can be implemented in various different ways, inparticular taking account of the nature of the organic medium mixed inthe precursor material. The organic medium in the mixture can beconstituted, in particular, by a thermoplastic medium, a thermosettingmedium, or a photopolymerizable medium.

Generally speaking, the method may be initiated in one or more of thefollowing ways. The first mixture may be placed on the first substrateprior to application of the mold in the forming operation (in a vacuumenclosure) or the mold may initially be placed on the first substrate, avacuum established, and then the mixture injected therein. If athermoplastic medium is used in the mixture, then the mixture maypreferably be initially heated, shaped with an appropriate mold, andallowed to cool, after which the mold may be removed. If the medium is athermosetting medium, then the mixture may be formed at ambienttemperature with an appropriate mold, heated once it has been formed,cooled, and then the mold may be removed. If the medium is aphotopolymerizable medium, then the mixture may be formed at ambienttemperature with an appropriate mold. Once it has been formed, it may beexposed to appropriate radiation (light, X-rays), after which the moldmay be removed. As one of skill in the art will recognize, molds usedmay be prepared and adapted to the desired final shape from suitablemaster molds, in conventional manner.

Vacuum-forming generates shapes in relief in the mixture of precursormedium and organic material. In characteristic manner, according to theinvention, the shapes are obtained by deforming the mixture while it issupported on a substrate. The substrate is preferably not subjected toany etching.

Since the presintering is preferably performed on a structure that issupported, it is simple to perform and the structure retains itsplaneness. Presintering serves to eliminate a major portion of theorganic components from the mixture prior to assembly (prior to closingthe structure). Eliminating volatile components from a complexthree-dimensional structure is always a problem, since the gases must beable to escape without damaging the structure. The use of substratesmade of glass, glass ceramic, ceramic, metal, or semiconductor isparticularly advantageous in that, sub-structures can be formed easilywithout the need to produce and handle such sub-structures in aself-supporting configuration which would be fragile, the structures donot sag or become distorted, thus making it possible to provide ribsthat are far apart and/or wall shapes that are complex, and it is easyto introduce additional parts such as electrical conductors, electrodes,or light conductors on the substrates with the mechanical behavior ofthe parts being good.

In conventional manner, presintering is generally implemented after amaterial that is inert relative to the precursor material, and thatabsorbs the organic medium has been applied to the formed mixture. Thisminimizes the extent to which the formed mixture sags or collapses. Theabsorbent material is generally powdered or sprayed onto the formedmixture for presintering.

When operations are not repeated, the method of the invention makes itpossible to provide a single stage device (by assembling together firstand second substrates; one of the substrates then acts as a bottom whilethe other acts as a cover plate). When operations are repeated, themethod makes it possible to provide a device comprising n stages, usingone or more common substrates. Such one or n stage devices can then besecured to one another by using a joining material, in particular anadhesive. Devices of the invention having one stage, n stages withcommon substrates, n stages stuck to one another (no common substrate),or n stages, some of them having common substrates and some of themhaving no common substrate, can all be used in a vertical position, in ahorizontal position, in an inclined position, or in some otherorientation known in the art.

The method of the invention for obtaining any element of the finaldevice can be implemented in three main variant manners according to thetype of cover plate involved. As mentioned above, the second (n^(th))substrate can be applied to the presintered mixture of the first(n−1^(th)) substrate, untreated, (although this variant is notpreferred, it is certainly not excluded), coated with an optionallypresintered second mixture, the second mixture is preferably in the formof a uniform layer that has not been shaped, it can optionally bepresintered and if it has not been presintered, then contact with thepresintered first mixture is improved, and coated with a second mixturethat has been vacuum-formed and presintered (like the first mixture).This exemplary implementation is advantageously performed with the twosubstrates in alignment in order to take advantage of the complementaryshapes formed as recesses in the mixtures. This makes it possible inmicrofluidic devices of the invention to obtain significant aspectratios, which ratios can be greater than 10.

In addition to the steps described above, the method of the inventioncan include additional steps. Passages may be provided by drilling toallow fluid circulation, to allow such fluids to enter and leave, orindeed to allow them to pass from a recess in one element to a recess inanother element. Drilling operations may also be performed on parts thatare to be assembled together, advantageously through the presinteredmixtures. In addition, one or more additional parts can be inserted, inparticular parts of the type specified above (electrical conductors,electrodes, light conductors) on one of the substrates involved and/orin the precursor mixture involved, or indeed in an intermediate layerthat is inserted between at least one of the first and second substratesand the corresponding first or second mixture. During manufacture ofeach of the elements of the device of the invention it is entirelypossible to slide at least one intermediate layer (a fine layer of Si, alayer of glass, of ceramic, or glass ceramic) between a substrate andthe precursor mixture for generating a portion of the one-piecemicrostructure, in particular, electrodes that can be formed byconventional printing, photolithography, or electroforming techniques.Actions can also be taken on the inside surfaces of the recess in theone-piece microstructure. This may be done for the purpose of depositinga catalyst, laying a film, or a coating, for example. In other words,chemical or physical treatment can be applied to the surfaces which areto come into contact with the fluids.

Reference will now be made in detail to the present preferredembodiments of the invention, examples of which are illustrated in theaccompanying drawing figures. Where ever possible, the same referencenumerals will be used throughout the drawings to refer to the same orlike parts.

Exemplary embodiments of a method of manufacturing a microfluidic devicein accordance with the present invention is shown in FIG. 1.

Initially and in a preferred embodiment, microstructures in relief aremade on a substrate A (e.g. of glass or of silicon) with saidmicrostructures being made by molding a mixture C₀ comprising glass fritand a thermoplastic medium (for example). Two different techniques areshown diagrammatically. The technique in the upper right corner of FIG.1 is similar to the technique described in U.S. Pat. No. 5,853,446, andmore particularly to the method described in Example 4 of that patent.In accordance with the method, mixture C₀ is deposited on the substrateA. Substrate A carrying the mixture is placed on a thermostaticallycontrolled support 1. A suitable mold made of elastomer 4 is prepared inadvance. The mold is positioned on a support 3, which is itself securedto a heater element 2. The assembly comprising elements 2, 3, and 4 isdegassed in a vacuum inside the enclosure 5 prior to being applied tothe mixture C₀ in the enclosure. Such degassing preferably degasses themixture C₀ and prevents any bubbles of gas from being trapped in theformed mixture.

The method in the upper left corner of FIG. 1 is based on injectingmixture C₀ into the mold 4 after it has been placed in advance on thesubstrate A. The assembly including the substrate A and the mold 4 ispositioned between two hot plates 31 inside a jacket 32 suitable foropening and closing under the action of a piston 33. After the inside ofthe mold 4 has been evacuated by an evacuation mechanism 34, the mixtureC₀ is injected through the an injector 35. At the end of thethermoforming process, the thermoformed assembly is ejected usingejector mechanism 36 acting through the bottom hot plate.

After the vacuum-forming step has been implemented, a mixture C₁ isobtained that is secured to substrate A, which mixture includes mixtureC₀ that has been thermoformed. The assembly is then subjected to heattreatment so that mixture C₁ is presintered. It is then referenced C₂and consists mainly of heat-treated glass frit.

In parallel, a cover plate is prepared for the intended device. In afirst embodiment, the cover plate includes a substrate B (optionallyidentical to substrate A) which is placed untreated on C₂. The assemblyis then subjected to heat treatment under suitable conditions to causethe three components of the resulting microfluidic device 10, i.e. thesubstrates A and B with the fired one-piece microstructure C₃ betweenthem, to be securely united. Generally speaking, the microstructurepreferably includes recesses 6.

In a second embodiment, the cover plate includes a substrate B(optionally identical to the substrate A) coated in a uniform layer of amixture D of glass frit and a thermoplastic medium (for example).Mixture D is optionally presintered. It therefore optionally includessignificant quantities of thermoplastic medium. The resulting assemblyis subjected to heat treatment under appropriate conditions forgenerating a microfluidic device 10′ in accordance with the invention.Its microstructure C₃ plus D contains the recesses 6′.

In a third embodiment, the cover plate is of the same type as the bottomplate. It includes a substrate (the same substrate as A in the exampleshown) having a presintered thermoformed mixture secured thereto (thesame mixture C₂ in the embodiment shown). Thus, by placing the patternsin relief so that they are in register with each other, it is possibleto obtain recesses 6″ of large volume (and presenting significant aspectratios). The resulting assembly is subjected to heat treatment undersuitable conditions to generate a microfluidic device 10″ of theinvention.

To obtain the microfluidic device 100 that is shown in section in FIG.2A, which device includes three stages, three devices 10″ are preparedin succession. The three devices 10″ are not prepared independently,since the top substrate of the first stage constitutes the bottomsubstrate of the second stage, and the top substrate of the second stageconstitutes the bottom substrate of the third stage. The assembly isbuilt up stage by stage and then the final assembly is fired. A passage20 is provided between one of the recesses in the second stage and oneof the recesses in the third stage.

FIG. 2B is a section showing a device 101 of the invention that has fourstages (10′+10″+10″+10″) which are in horizontal alignment. The device101 is obtained from a three-stage device 100 (10″+10″+10″) as shown inFIG. 2A plus a single-stage device 10′ as shown in FIG. 1. Devices 100and 10′ are preferably connected together by adhesive. The joint ofadhesive material is given reference 40. Device 101 thus presents a“composite” type of structure (i.e. with assembly by means of a commonsubstrate, and with assembly by means of two substrates, all in the samestructure).

FIG. 3 is a section view of a single-element device of the invention ofthe 10″ type. The technique used makes it possible to generateadvantageous shapes for the recesses 21 and 22. The first recess, 21, issubstantially hexagonal in section while the second recess, 22, issubstantially circular in section. Such a section having no angles isparticularly advantageous.

FIG. 4 is a section showing a single-element device of the invention ofthe 10′ type. Its structure includes a passage 20 and an electricalconductor 23. The electrical conductor 23 is positioned on the bottomsubstrate A before depositing the mixture C₀. By using suitabletreatment, the surface(s) of the recess 6′ is modified. The device ispreferably fed with fluid via the passage 20.

FIG. 5 is a perspective view of a single-element device of the inventionof the 10″ type. The device nevertheless also includes threeintermediate layers 50, 51, and 52 between the substrates A and theone-piece microstructure C₃. These intermediate layers 50, 51, and 52are involved with additional parts 24, 24′, 24″, and 24′″ of the typeincluding electrodes and light conductors. The parts 24 of the firstlayer 50 are disposed perpendicularly to the parts 24′ and 24″,respectively, in the third layer 52, and on the third layer 52. The part24″ lies on the third layer 52 in the microstructure C₃. The part 24′″,e.g. of the sensor type, opens out into the recess 6″.

EXAMPLE

The invention is illustrated by the following example:

Microreactors of the 10′ type (as shown diagrammatically in FIG. 4) weremade using a baseplate of alkali-lime type glass on which electrodeswere deposited (which electrodes can be used for local heating, fortemperature control, or as probes). The thickness of the first substrateshould be at least 200 μm, and should generally lie in the range ofabout 200 μm to about 3 millimeters (mm). Structures in relief wereformed on the glass plate by microforming glass, the structures having awidth lying in the range of about 100 μm to about 300 μm and a height ofup to approximately 800 μm; the widths of the resulting capillaries(i.e. recesses) lay in the range of about 50 μm to more than about 1000μm. Passages were drilled in the appropriate locations to put recessesof the device into communication with the outside. Thereafter, a coverplate of alkali-lime glass was put into place on the drilled glass plate(the cover plate constituting a second substrate and likewise having athickness of at least about 200 μm, and generally lying in the range ofabout 200 μm to about 3 mm). The cover plate was covered in a smoothlayer of glass substantially identical to the glass used on thebaseplate. The assembly was heated to seal the recesses of thestructure.

More specifically, the following steps were performed in succession:

First Step: Provision of a Suitable Mold.

In this example, a mold was made of flexible silicone (RTV 141). To makesuch a mold, it was necessary to have a master mold of metal, polymer orglass, for example (the master mold itself being obtained by a methodsuch as mechanical machining, electro-erosion, stereolithography). Theparticular master mold used was made by photolithography using a thickSU8 photo resist.

Second Step: Preparing the First Glass Precursor Mixture.

The first mixture included glass frit (VR 725 from CERDEC) and athermoplastic medium (MX 4462 from CERDEC) with an inorganic overorganic ratio greater than about 4 by weight. It was obtained merely bymixing.

Third Step: Making Electrodes on the First Substrate.

The first substrate (baseplate) was selected to have a softeningtemperature higher than that of the glass frit (VR 725). The electrodeswere made by silk-screen printing a silver paste (CERDEC Ref. 7435) inthe selected pattern. The deposited paste was presintered atapproximately 500° C.

Fourth Step: Forming the First Mixture.

The first mixture was deposited on the glass baseplate at a temperatureof about 100° C. The silicone mold was also maintained at about 100° C.It was positioned facing the plate. The assembly was then placed in avacuum. The mold was applied to the first mixture with a force of about0.1 kilograms per square centimeter (kg/cm²). The assembly was thenallowed to cool to ambient temperature, and the silicone mold was peeledoff.

Fifth Step: Making the Cover Plate.

A layer of about 10 μm to about 50 μm of a second mixture wasspun-coated onto a plate of alkali-lime glass. The second mixture waslikewise glass frit (VR 725) and a thermoplastic medium (MX 54 fromCERDEC).

Sixth Step: Presintering.

The thermoplastic media were eliminated from the baseplate and the coverplate by heat treatment. The heat treatment was implemented at 500° C.in a kiln. The temperature cycle was as follows:

2 hours (h) temperature rise from about 20° C. to about 500° C.;

1 h steady at about 500° C.; and

2 h temperature reduction from about 500° C. to about 20° C.

In conventional manner, the structures were prevented from collapsingduring the temperature rise. An absorbent material that does not reactwith glass frit, such as alumina powder was dusted onto the structures.This can be done, for example, in the manner described in Example 4 ofU.S. Pat. No. 5,853,446.

Seventh Step: Drilling.

The drilling was performed conventionally, using diamond drill bits. Bitdiameter was naturally the same as the diameter desired for the variouspassages. This diameter generally lies in the range of about 0.5 mm toabout 3 mm.

Eighth Step: Assembly and Firing

The cover plate was placed on the baseplate (the baseplate could equallywell be placed on the cover plate). Glass-glass bonding was achieved bysubjecting the assembly to the following temperature cycle:

2 h temperature rise from about 20° to about 550° C.;

20 minutes (min) steady at about 550° C.;

10 min temperature drop from about 550° C. to about 500° C.; and

2 h temperature drop from about 500° C. to about 20° C.

While the invention has been described in detail, it is to be expresslyunderstood that it will be apparent to persons skilled in the relevantart that the invention may be modified without departing from the spiritor scope of the invention. Various changes of form, design, orarrangement may be made to the invention without departing from thespirit and scope of the invention. Therefore, the above-mentioneddescription is to be considered exemplary, rather than limiting, and thetrue scope of the invention is that defined by the following claims.

What is claimed is:
 1. A method of manufacturing a microfluidic device, the method comprising the steps of: shaping a mixture including a binder and a precursor material on a first substrate; presintering the mixture and the substrate to remove the binder and form a consolidated first assembly; assembling the first assembly with a second assembly comprising a second substrate such that the presintered mixture is positioned between the first substrate and the second assembly; and heating the assembled first assembly and second assembly to a temperature sufficient to form a one-piece microstructure defining at least one recess between the first and second substrates.
 2. The method of claim 1 wherein the step of shaping the mixture on the first substrate includes placing a mold on the first substrate.
 3. The Method of claim 2 wherein the step of shaping the mixture on the first substrate further includes injecting the mixture into the mold.
 4. The Method of claim 3 wherein the step of shaping the mixture on the first substrate further includes establishing a vacuum between the mold and the first substrate before injecting the mixture into the mold.
 5. The method of claim 1 wherein the second assembly further comprises a uniform layer of a mixture including a binder and a precursor material applied to the second substrate and wherein the assembling step comprises the step of affixing the uniform layer of the mixture to the presintered mixture.
 6. The method of claim 1 wherein the second assembly further comprises a presintered shaped mixture secured to the second substrate and wherein the assembling step comprises the step of positioning the presintered mixture of the first assembly adjacent the presintered mixture of the second assembly.
 7. The method of claim 1 further comprising the step of drilling at least one passage to provide communication between the outside and the at least one recess.
 8. The method of claim 1 further comprising the step of repeating the shaping, presintering, assembling, and heating steps to form a plurality of one-piece microstructures and joining the plurality of one-piece microstructures such that they have at least one substrate in common.
 9. The method of claim 1 further comprising the step of positioning a part selected from the group consisting essentially of electrical conductors, electrodes and light conductors on an intermediate layer positioned between the first substrate and the mixture.
 10. The method of claim 1 wherein the binder is an organic binder.
 11. A microfluidic device made by the process claimed in claim
 1. 